Mean Left Ventricular Wall Thickness Research Articles

Artesunate attenuates isoprenaline induced cardiac hypertrophy in rats via SIRT1 inhibiting NF-κB activation

Cardiac Hypertrophy is an adaptive response of the body to physiological and pathological stimuli, which increases cardiomyocyte size, thickening of cardiac muscles and progresses to heart failure. Downregulation of SIRT1 in cardiomyocytes has been linked with the pathogenesis of cardiac hypertrophy. The present study aimed to investigate the effect of Artesunate against isoprenaline induced cardiac hypertrophy in rats via SIRT1 inhibiting NF-κB activation. Experimental cardiac hypertrophy was induced in rats by subcutaneous administration of isoprenaline (5 mg/kg) for 14 days. Artesunate was administered simultaneously for 14 days at a dose of 25 mg/kg and 50 mg/kg. Artesunate administration showed significant dose dependent attenuation in mean arterial pressure, electrocardiogram, hypertrophy index and left ventricular wall thickness compared to the disease control group. It also alleviated cardiac injury biomarkers and oxidative stress. Histological observation showed amelioration of tissue injury in the artesunate treated groups compared to the disease control group. Further, artesunate treatment increased SIRT1 expression and decreased NF-kB expression in the heart. The results of the study show the cardioprotective effect of artesunate via SIRT1 inhibiting NF-κB activation in cardiomyocytes.

Genotipe-phenotype correlation in alpk3 null variants. an extended analysis

Abstract Introduction ALPK3 null variants (ALPK3nv) in simple heterozygosis represent an established and emerging genetic cause for hypertrophic cardiomyopathy. Some studies have indicated that this genetic substrate would be associated with a disease of late-onset disease and incomplete penetrance. Purpose To perform an extended genotype-phenotype correlation analysis with respect to simple heterozygous ALPK3nv carriers, focusing on age at diagnosis, maximum wall thickness and survival analysis, performed on the largest available released cohort to date. Methods ALPK3 gene was included in an extended NGS panel in 16,780 probands from a reference multicentric genetic laboratory, of whom 6,505 were referred with a HCM phenotype. We collected a composite cohort of ALPK3nv (considering frameshift, nonsense and splice-site predicted frameshift variants), including index and familial cases referred to this laboratory, but also cases reported in the literature. Phenotypic behavior was analyzed, mainly considering age at diagnosis, maximum LV wall thickness, and a composite of events (heart failure and arrhythmia-related endpoints). Results A heterozygous ALPK3 null variant was identified in 110 probands out of 6,505 index cases diagnosed with HCM in our center (1.7% of HCM cases). For genotype-phenotype analysis, in total 189 heterozygous carriers were included, considering relatives and cases from the literature; 21 carriers had biallelic involvement (were homozygous or compound heterozygous for two ALPK3Knv). Among ALPK3nv heterozygous carriers, mean age at diagnosis was 53.4 (±15.2) years; mean left ventricular thickness was 17.7 (±4.9) mm, and morphological profile was mainly apical (42%) and/or concentric (26%). Males tended to be diagnosed at an earlier age than females (median age of diagnosis was 56 vs 71 years, respectively, p <0.01). Five events were observed in this group (four males and one female) all of them related to heart failure, and occur in carriers older than 45 years. The clinical profile was drastically different in cases with biallelic involvement, with a mean age at diagnosis of 22.2±9.3, mean LV wall thickness of 24 mm (±8.6), with LV dysfunction observed in 25%. Nine events were observed in this group, also mostly associated with HF (70%). Conclusions ALPK3 null variants in simple heterozygosis can explain 1.7% of HCM. They were associated with late-onset disease, especially in females, predominance of apical and/or concentric forms, and a phenotype that was not particularly severe, both morphologically and in terms of survival.

Novel Findings of Early Cardiac Dysfunction in Patients With Childhood-Onset Inflammatory Bowel Disease Using Layer-Specific Strain Analysis.

Patients with inflammatory bowel disease (IBD) are at a higher risk of developing cardiovascular diseases than healthy individuals, owing to persistent chronic inflammation and treatment effects. This study aimed to assess left ventricular function in patients with childhood-onset IBD using layer-specific strain analysis and to identify early indicators of cardiac dysfunction in them. A total of 47 patients with childhood-onset ulcerative colitis (UC), 20 patients with Crohn's disease (CD), and 75 age- and sex-matched healthy control subjects were included in this study. Conventional echocardiographic measurements of layer-specific (ie, endocardium, midmyocardium, and epicardium) global longitudinal strain and global circumferential strain (GCS) were evaluated in these participants. Layer-specific strain analysis showed that global longitudinal strain was lower in all layers for the UC (P < .001) and CD (P < .001) groups, regardless of the age at onset, but that GCS was only lower in the midmyocardial (P = .032) and epicardial (P = .018) layers in the CD group than in the control group. Although the mean left ventricular wall thickness was not significantly different among the groups, it was significantly correlated with the GCS of the endocardial layer in the CD group (ρ= -0.615; P = .004), suggesting that thickening of the left ventricular wall occurred as a compensatory mechanism to maintain the endocardial strain in the CD group layer. Children and young adults with childhood-onset IBD displayed decreased midmyocardial deformation. Layer-specific strain could also be useful to identify indicators of cardiac dysfunction in patients with IBD.

An Integrated Algorithm for Differentiating Hypertrophic Cardiomyopathy From Hypertensive Heart Disease.

Differentiating hypertrophic cardiomyopathy (HCM) from hypertensive heart disease (HHD) is challenging. To identify differences between HCM and HHD on a patient basis using MRI. Retrospective. A total of 219 subjects, 148 in phase I (baseline data and algorithm development: 75 HCM, 33 HHD, and 40 controls) and 71 in phase II (algorithm validation: 56 HCM and 15 HHD). Contrast-enhanced inversion-prepared gradient echo and cine-balanced steady-state free precession sequences at 3.0 T. MRI parameters assessed included left ventricular (LV) ejection fraction (LVEF), LV end systolic and end diastolic volumes (LVESV and LVEDV), mean maximum LV wall thickness (MLVWT), LV global longitudinal and circumferential strain (GRS, GLS, and GCS), and native T1. Parameters, which were significantly different between HCM and HHD in univariable analysis, were entered into a principal component analysis (PCA). The selected components were then introduced into a multivariable regression analysis to model an integrated algorithm (IntA) for screening the two disorders. IntA performance was assessed for patients with and without LGE in phase I (development) and phase II (validation). Univariable regression, PCA, receiver operating curve (ROC) analysis. A P value <0.05 was considered statistically significant. Derived IntA formulation included LVEF, LVESV, LVEDV, MLVWT, and GCS. In LGE-positive subjects in phase l, the cutoff point of IntA ≥81 indicated HCM (83% sensitivity and 91% specificity), with the area under the ROC curve (AUC) of 0.900. In LGE-negative subjects, a higher possibility of HCM was indicated by a cutoff point of IntA ≥84 (100% sensitivity and 82% specificity), with an AUC of 0.947. Validation of IntA in phase II resulted in an AUC of 0.846 in LGE-negative subjects and 0.857 in LGE-positive subjects. A per-patient-based IntA algorithm for differentiating HCM and HHD was generated from MRI data and incorporated FT, LGE and morphologic parameters. 3. Stage 2.

Cardiopulmonary Exercise Testing in Athletes With Hypertrophic Cardiomyopathy

Patients with hypertrophic cardiomyopathy (HCM) have historically been restricted from athletic participation because of the perceived risk of sudden cardiac death. More contemporary research has highlighted the relative safety of competitive athletics with HCM. However, lack of published data on reference values for cardiopulmonary exercise testing (CPET) complicates clinical management and counseling on sports participation in the individual athlete. We conducted a single-center, retrospective cohort study to investigate CPET in athletes with HCM and clinical characteristics associated with objective measures of aerobic capacity. We identified 58 athletes with HCM (74% male, mean age 18±3years, mean left ventricular (LV) wall thickness 20±7mm). LV outflow tract obstruction was present in 22 (38%). A total of 15 (26%) athletes were taking a β blocker (BB), but only 4 (7%) reported exertional symptoms. Overall, exercise capacity was mildly reduced, with a peak myocardial oxygen consumption (peak VO2) of 37.9ml/min/kg (83% of predicted peak VO2). Both LV outflow tract obstruction and BB use were associated with reduced exercise capacity. Limited peak heart rate was more common in athletes taking BB (47% vs 9%, p=0.002). At a mean 5.6years follow-up, 5 patients underwent myectomy (9%), and 8 (14%) received an implantable cardioverter defibrillator (ICD) for primary prevention. One individual with massive LV hypertrophy experienced recurrent ICD shocks for ventricular fibrillation and underwent myectomy 7years after initial evaluation and was no longer participating in sports. There were no deaths over the follow-up period. In conclusion, the prognostic role of CPET remains unclear in athletes with HCM. Mildly reduced exercise capacity was common; however, reduced peak VO2 did not correlate with symptom status or clinical outcomes. A significant proportion went on to require myectomy and/or ICD, thus highlighting the need for close follow-up. These data provide some initial insight into the clinical evaluation of "real world" athletes with HCM; however, further study is warranted to help guide shared decision-making, return-to-play discussions, and the potential long-term safety of competitive athletic participation.

Intensive compared with less intensive blood pressure control to prevent adverse cardiac remodelling in children with chronic kidney disease (HOT-KID): a parallel-group, open-label, multicentre, randomised, controlled trial

Optimal target blood pressure to reduce adverse cardiac remodelling in children with chronic kidney disease is uncertain. We hypothesised that lower blood pressure would reduce adverse cardiac remodelling. HOT-KID, a parallel-group, open-label, multicentre, randomised, controlled trial, was done in 14 clinical centres across England and Scotland. We included children aged 2-15 years with stage 1-4 chronic kidney disease-ie, an estimated glomerular filtration rate (eGFR) higher than 15 mL/min per 1·73 m2-and who could be followed up for 2 years. Children on antihypertensive medication were eligible as long as it could be changed to angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) if they were not already receiving these therapies. Participants were randomly assigned (1:1) to standard treatment (auscultatory office systolic blood pressure target between the 50th and 75th percentiles) or intensive treatment (systolic target <40th percentile) by the chief investigator using a rapid, secure, web-based randomisation system. ACE inhibitors or ARBs were used as first-line agents, with the dose titrated every 2-4 weeks to achieve the target blood pressure levels. The primary outcome was mean annual difference in left ventricular mass index (LVMI) by echocardiography measured by a masked observer and was assessed in the intention-to-treat population, defined as all the children who underwent randomisation irrespective of the blood pressure reached. Secondary and safety outcomes were the differences between groups in mean left ventricular relative wall thickness, renal function, and adverse effects and were also assessed in the intention-to-treat population. This trial is registered with ISRCTN, ISRCTN25006406. Between Oct 30, 2012, and Jan 5, 2017, 64 participants were randomly assigned to the intensive treatment group and 60 to the standard treatment group (median age of participants was 10·0 years [IQR 6·8-12·6], 69 [56%] were male and 107 [86%] were of white ethnicity). Median follow-up was 38·7 months (IQR 28·1-52·2). Blood pressure was lower in the intensive treatment group compared with standard treatment group (mean systolic pressure lower by 4 mm Hg, p=0·0012) but in both groups was close to the 50th percentile. The mean annual reduction in LVMI was similar for intensive and standard treatments (-1·9 g/m2·7 [95% CI -2·4 to -1·3] vs -1·2 g/m2·7 [-1·5 to 0·8], with a treatment effect of -0·7 g/m2·7 [95% CI -1·9 to 2·6] per year; p=0·76) and mean value in both groups at the end of follow-up within the normal range. At baseline, elevated relative wall thickness was more marked than increased LVMI and a reduction in relative wall thickness was greater for the intensive treatment group than for the standard treatment group (-0·010 [95% CI 0·015 to -0·006] vs -0·004 [-0·008 to 0·001], treatment effect -0·020 [95% CI -0·039 to -0·009] per year, p=0·0019). Six (5%) participants reached end-stage kidney disease (ie, an eGFR of <15 mL/min per 1·73 m2; three in each group) during the course of the study. The risk difference between treatment groups was 0·02 (95% CI -0·15 to 0·19, p=0·82) for overall adverse events and 0·07 (-0·05 to 0·19, p=0·25) for serious adverse events. Intensive treatment was not associated with worse renal outcomes or greater adverse effects than standard treatment. These results suggest that cardiac remodelling in children with chronic kidney disease is related to blood pressure control and that a target office systolic blood pressure at the 50th percentile is close to the optimal target for preventing increased left ventricular mass. British Heart Foundation.

Patterns of Left Ventricular Hypertrophy and Late Gadolinium Enhancement onCardiac Magnetic Resonanace in Patients with Hypertrophic Cardiomyopathy

Objective: To evaluate the patterns of left ventricular hypertrophy (LVH) and late gadolinium enhancement (LGE) inhypertrophic cardiomyopathy.&#x0D; Study Design: Analytical cross-Sectional Study.&#x0D; Place and Duration of Study: Tertiary Cardiac Care Center, Rawalpindi Pakistan from 01 June 2020 to 30 Dec 2021.&#x0D; Methodology: This study was carried out at a tertiary cardiac care center retrospectively from 1 June 2020 to 31 December 2021. Patients having LV hypertrophy due to aortic stenosis, hypertension, athlete’s heart, and infiltrative disorders were excluded from study. Cases were included using nonprobability consecutive sampling. Sample size estimated by taking 0.2- 0.5 % (1 in 200-500) prevalence of hypertrophic cardiomyopathy using open epi sample size calculator was (n=38) taking 99.99% confidence interval. For the purpose of study all patients with confirmed HCM undergoing CMR during given period were included in study.Approval from the ethical review committee with IERB (IERB letter # 9/2/R&amp;D/2022/179) was sought. CMR was performed using MRI 3 Tesla. Data analysis was done on SPSS version-26. Quantitative variables were expressed as Mean±SD. Qualitative variables were expressed as frequencies and percentages. ANOVA and student t-test (95% CI and 5% margin of error) was applied to compare the study variables. p-vale &lt;0.05 was considered statistically significant.&#x0D; Results: Majority 77(86.7%) of patients were males. Most common pattern of involvement for LV hypertrophy was asymmetrical septal hypertrophy in 47 (52.8%) followed by apical HCM in 29(32.6%). LVOT obstruction was observed in 30(33.7%) of patients. Mean maximum LV wall thickness was 22mm±5.47.&#x0D; Conclusion: Our study shows association, between the extent of Late Gadolinium Enhancement and LV wall thickness, myocardial mass index in HCM patients.

Prognosis of Transthyretin Cardiac Amyloidosis Without Heart Failure Symptoms

BackgroundTransthyretin amyloid cardiomyopathy (ATTR-CM) is increasingly recognized as a treatable cause of heart failure (HF). Advances in diagnosis and therapy have increased the number of patients diagnosed at early stages, but prognostic data on patients without HF symptoms are lacking. Moreover, it is unknown whether asymptomatic patients benefit from early initiation of transthyretin (TTR) stabilizers. ObjectivesThe aim of this study was to describe the natural history and prognosis of ATTR-CM in patients without HF symptoms. MethodsClinical characteristics and outcomes of patients with ATTR-CM without HF symptoms were retrospectively collected at 6 international amyloidosis centers. ResultsA total of 118 patients (78.8% men, median age 66 years [IQR: 53.8-75 years], 68 [57.6%] with variant transthyretin amyloidosis, mean left ventricular ejection fraction 60.5% ± 9.9%, mean left ventricular wall thickness 15.4 ± 3.1 mm, and 53 [45%] treated with TTR stabilizers at baseline or during follow-up) were included. During a median follow-up period of 3.7 years (IQR: 1-6 years), 38 patients developed HF symptoms (23 New York Heart Association functional class II and 14 functional class III or IV), 32 died, and 2 required cardiac transplantation. Additionally, 20 patients received pacemakers, 13 developed AF, and 1 had a stroke. Overall survival was 96.5% (95% CI: 91%-99%), 90.4% (95% CI: 82%-95%), and 82% (95% CI: 71%-89%) at 1, 3, and 5 years, respectively. Treatment with TTR stabilizers was associated with improved survival (HR: 0.31; 95% CI: 0.12-0.82; P = 0.019) and remained significant after adjusting for sex, age, ATTR-CM type, and estimated glomerular filtration rate (HR: 0.18; 95% CI: 0.06-0.55; P = 0.002). ConclusionsAfter a median follow-up period of 3.7 years, 1 in 3 patients with asymptomatic ATTR-CM developed HF symptoms, and nearly as many died or required cardiac transplantation. Treatment with TTR stabilizers was associated with improved prognosis.

Independent prognostic value of left ventricular mass index in patients with light-chain amyloidosis

Background Echocardiographic-determined left ventricular mass index (LVMI) provides quantitative information on left-ventricular structure. However, its prognostic value on light-chain (AL) amyloidosis has not been clearly defined. Methods We included 99 patients with newly diagnosed AL amyloidosis between July 2013 and March 2022. Clinical features and echocardiographic parameters were collected. Results LVMI ≥113.4 g/m2 was predictive for overall survival (OS) and progression-free survival (PFS) with respective hazard ratios (HRs) of 2.87 (95% CI: 1.04–7.79) and 2.91 (95% CI: 1.25–6.68). Patients in the LVMI-high group had higher NT-proBNP, cTnT, and FLC-diff levels. They were more likely to be cardiac involved and have increased mean left ventricular wall thickness, decreased left ventricular ejection fraction, and higher proportion of patients with pericardial effusion. In subgroup analysis, LVMI-high group was associated with a reduced OS [HR: 4.74 (95% CI: 1.26–17.77)] and PFS [HR: 7.16 (95% CI: 2.10–24.40)] in patients with cardiac amyloidosis (CA). Besides, LVMI-high was associated with a reduced OS [HR: 3.58 (95% CI: 1.17–11.02)] and PFS [HR: 4.79 (95% CI: 1.77–12.94), p = 0.00] among patients staged of II or III (Mayo 2004), as well as reduced OS [HR: 22.65 (95% CI: 1.66–299.31)] and PFS [HR: 18.73 (95% CI: 2.36–148.35)] among patients staged of III or IV (Mayo 2012). Conclusions LVMI is a reliable prognostic indicator of survival. A cut-off of LVMI (113.4 g/m2) was prognostic for OS and PFS. Importantly, LVMI was able to identify a subset of patients with poorer prognosis in the context of CA or in the late stages according to the biomarker staging systems.

New-onset atrial fibrillation diagnosed by cardiac implantable devices in patients with hypertrophic cardiomyopathy: a systematic review and meta-analysis

Abstract Background Atrial fibrillation (AF) in patients with hypertrophic cardiomyopathy (HCM) is associated with high thromboembolic risk, morbidity, and mortality. Purpose We aimed to study the role of cardiac implantable devices (CID) for AF diagnosis in patients with HCM without prior AF history. Methods A comprehensive systematic review and meta-analysis was conducted using Pubmed, Embase, and ClinicalTrials.gov through November 2021 for studies reporting incidence of new-onset AF detected by CID including implantable cardioverter defibrillators, pacemakers, cardiac resynchronization therapy, and loop recorder devices in HCM patients. We used a Freeman-Tukey transformation to calculate the weighted summary proportion of the incidence of AF and stroke and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using a random-effects model. Results Eight cohort studies were included, totalizing 910 patients with HCM and CID without baseline AF. Mean age was 54 years and 21% were female. Mean left ventricular wall thickness was 22.6 mm. Mean follow-up was 3.1 years. New-onset AF was detected in 27.6% (95% CI 18.7–37.5) of patients (Figure A) and 84% of the episodes were subclinical. Stroke occurred in 4.7% (95% CI 1.8–9.0) of patients without baseline AF (Figure B). There was no significant difference in the unadjusted risk of stroke between patients with newly diagnosed AF vs no AF detected at the end of follow-up (9.4% vs 4.7%, OR 1.93, 95% CI 0.83–4.48, p=0.13). Conclusion There is a high incidence of subclinical new-onset AF in patients with HCM, supporting the use of CID for early detection of AF in this population. Funding Acknowledgement Type of funding sources: None.

Comparison of Cardiac Wall Thicknesses and Coronary Artery Obstructions Between Deaths Resulting From Acute Myocardial Infarction and Deaths From Other Causes.

Objective:The risk factors for myocardial infarction (MI) can be separated into three general categories: non-modifiable factors, modifiable risk factors, and lifestyle. This study aimed to investigate whether or not there was any effect of cardiac wall thickness and coronary artery obstructions on acute MI.Methods:In this retrospective study of histopathological examinations of autopsies, two groups were formed. The first contained 28 cases diagnosed with acute MI and the second 28 cases with no heart pathology and the cause of death was reasons other than heart disease. The subjects in the two groups were similar in age, height, weight, and body mass index. The groups were compared in terms of the left and right ventricular wall thicknesses and the degree of obstruction of the right, left, anterior descending, and circumflex coronary arteries.Results:The mean left ventricular wall thickness was 1.461±0.2767 cm in the acute MI group and 1.386±0.2460 cm in the control group, with no statistically significant difference found between the two groups (p=0.289). A statistically significant difference in the degree of obstruction of the coronary arteries was found between the groups.Conclusions:Although the mean cardiac wall thickness was greater in the acute MI cases, no statistically significant difference was found between the two groups.

Hypertrophic Cardiomyopathy and Pregnancy: A Retrospective Analysis From a Tertiary Care Hospital.

Pregnancy in women with hypertrophic cardiomyopathy is not well described. In this retrospective study, we analyzed data on pregnant women with hypertrophic cardiomyopathy who were under follow-up care in the cardiology department of a tertiary care hospital. We reviewed data on all women registered in the hypertrophic cardiomyopathy cohort and those who attended the cardio-obstetric clinic and delivered between January 2010 and June 2019. From these 2 groups, we identified 7 pregnant women with hypertrophic cardiomyopathy who delivered during this period. These 7 women (mean [SD] age, 25 [3.3] years) had a total of 15 pregnancies (range per woman,1-4). This was a high-risk cohort, as 7 (46.7%) pregnancies were in the modified World Health Organization class III. The mean (SD) left ventricular wall thickness was 19.71 (2.56) mm in all pregnancies. Two of the 7 women with left ventricular outflow tract obstruction developed severe symptoms in the third trimester; these improved soon after delivery. Eight pregnancies without obstruction were well tolerated. Two pregnancies occurred after successful alcohol septal ablation. Both remained asymptomatic throughout pregnancy. All women tolerated labor well. Adverse maternal outcomes, including death, were not seen in any patient. All women who became symptomatic during pregnancy had relief of symptoms after delivery. Most women remained asymptomatic or had mild symptoms during pregnancy. Of the women with left ventricular outflow tract obstruction, 28.6% had severe symptoms that improved after delivery. Pregnancy was well tolerated after successful alcohol septal ablation.

Enhanced nuclear localization of phosphorylated MLKL predicts adverse events in patients with dilated cardiomyopathy.

The role of necroptosis in dilated cardiomyopathy (DCM) remains unclear. Here, we examined whether phosphorylation of mixed lineage kinase domain-like protein (MLKL), an indispensable event for execution of necroptosis, is associated with the progression of DCM. Patients with DCM (n=56, 56±15years of age; 68% male) were enrolled for immunohistochemical analyses of biopsies. Adverse events were defined as a composite of death or admission for heart failure or ventricular arrhythmia. Compared with the normal myocardium, increased signals of MLKL phosphorylation were detected in the nuclei, cytoplasm, and intercalated discs of cardiomyocytes in biopsy samples from DCM patients. The phosphorylated MLKL (p-MLKL) signal was increased in enlarged nuclei or nuclei with bizarre shapes in hypertrophied cardiomyocytes. Nuclear p-MLKL level was correlated negatively with septal peak myocardial velocity during early diastole (r=-0.327, P=0.019) and was correlated positively with tricuspid regurgitation pressure gradient (r=0.339, P=0.023), while p-MLKL level in intercalated discs was negatively correlated with mean left ventricular wall thickness (r=-0.360, P=0.014). During a median follow-up period of 3.5years, 10 patients (18%) had adverse events. To examine the difference in event rates according to p-MLKL expression levels, patients were divided into two groups by using the median value of nuclear p-MLKL or intercalated disc p-MLKL. A group with high nuclear p-MLKL level (H-nucMLKL group) had a higher adverse event rate than did a group with low nuclear p-MLKL level (L-nucMLKL group) (32% vs. 4%, P=0.012), and Kaplan-Meier survival curves showed that the adverse event-free survival rate was lower in the H-nucMLKL group than in the L-nucMLKL group (P=0.019 by the log-rank test). Such differences were not detected between groups divided by a median value of intercalated disc p-MLKL. In δ-sarcoglycan-deficient (Sgcd-/- ) mice, a model of DCM, total p-MLKL and nuclear p-MLKL levels were higher than in wild-type mice. The results suggest that increased localization of nuclear p-MLKL in cardiomyocytes is associated with left ventricular diastolic dysfunction and future adverse events in DCM.

Reference ranges for functional and structural echocardiographic parameters in asian athletes: a systematic review and meta-analysis

Abstract Funding Acknowledgements Type of funding sources: None. Background/Introduction Physiologic cardiac remodelling is common in elite athletes, including changes such as increased left ventricle size and left ventricular wall thickness. These changes often overlap with those from pathological cardiac conditions - for instance dilated cardiomyopathy and hypertrophic cardiomyopathy - leading to diagnostic uncertainty. The availability of reference ranges specific to elite athletes, particularly Caucasian and Black ethnicities, facilitates accurate differentiation between physiology and pathology. However, there remains a paucity of Asian data despite an increased representation in global sport. Purpose To perform a systematic review and meta-analysis of cardiac imaging studies in Asian elite athletes and obtain reference values for commonly utilised parameters in this population. Methods We searched MEDLINE via PubMed, Embase, and the Cochrane Database for relevant studies from inception till 27th July 2021. We included observational studies that reported relevant cardiac imaging parameters in Asian elite athletes. We excluded studies that did not report gender-specific cardiac imaging parameters. After study selection and data extraction, we performed random effects meta-analysis of means to obtain the weighted mean of each relevant cardiac imaging parameter stratified by gender. Results We included a total of eight studies with relevant echocardiographic data from East Asia, South Asia and West Asia which comprised a total of 799 male and 206 female elite athletes participating in endurance and mixed sport disciplines. We excluded data pertaining to athletes participating in skill and power disciplines in a post-hoc manner due to paucity of data and extreme data ranges. The weighted mean left ventricular mass (g) was 211.5 (95% CI 202.6 - 220.3, I2 = 85.8%) for males, and 139.3 (95% CI 132 - 146.7, I2 = 88.2%) for females. The weighted mean left ventricular mass indexed to body surface area (g/m2) was 103.1 (95% CI 99.2 - 106.9, I2 = 79.4%) for males, and 75.1 (95% CI 71.5 - 78.6, I2 = 86.1%) for females. For left ventricular end diastolic diameter (mm), the weighted mean was 54.4 (95% CI 53.1 - 55.7, I2 = 97.3%) for males, and 47.2 (95% CI 46.2 - 48.3, I2 = 89.3%) for females. Lastly, the weighted mean left ventricular wall thickness (mm) was 9.9 (95% CI 9.6 - 10.2, I2 = 91.3%) for males, and 8.7 (95% CI 8.5 - 9, I2 = 80.7%) for females. Conclusions This is the first meta-analysis that provides preliminary echocardiographic reference ranges for Asian elite athletes. Statistical heterogeneity, however, is high in most outcome measures. This is likely due to the presence of confounders such as study demographics. Due to a paucity of studies, further subgroup or stratified analyses could not be performed meaningfully. More large-scale observational studies are required such that more sport, gender or region-specific data could be generated.

Sex-related Differences In Cardiac Involvement In Wild-type Transthyretin Amyloidosis

<h3>Introduction</h3> Transthyretin amyloidosis (ATTR amyloidosis) is a rare but life-threatening disease that may arise from mutations in the transthyretin (<i>TTR</i>) gene (ATTRv amyloidosis) or from nonmutated, wild-type TTR (ATTRwt amyloidosis). Evidence suggests that female sex may be protective against cardiac involvement in ATTRv amyloidosis, but sex differences in cardiac involvement in ATTRwt amyloidosis have not been assessed. <h3>Hypothesis</h3> Cardiac involvement in patients with ATTRwt amyloidosis differs by sex. <h3>Methods</h3> The Transthyretin Amyloidosis Outcomes Survey (THAOS) is a global, longitudinal, observational survey of patients with ATTR amyloidosis, including both inherited and wild-type disease, and asymptomatic patients with <i>TTR</i> mutations (NCT00628745). Data from THAOS (data cutoff: January 4, 2021) were analyzed to evaluate sex-based differences in cardiac symptoms in patients with ATTRwt amyloidosis. <h3>Results</h3> There were 1272 patients (females, n=76; males, n=1196) with ATTRwt amyloidosis enrolled in THAOS. Median age at enrollment (80.7 vs 77.6 years; <i>P</i><0.05) and symptom onset (75.5 vs 73.0 years; <i>P</i><0.05) were higher in females vs males, whereas median time from symptom onset to diagnosis was similar between the groups (1.09 vs 1.55 years). Females had a significantly higher mean left ventricular (LV) ejection fraction (53% vs 48%; <i>P</i><0.05). The lower mean LV wall thickness (16 vs 17 mm) and mean LV mass index (161 vs 189 g/m²) observed in females vs males were not statistically significant. LV wall thickness (mm) divided by height (m) was similar in females vs males (9.8 vs 9.6). Sex was not found to be a predictor of mean LV wall thickness divided by height in a linear regression analysis. <h3>Conclusions</h3> Females with ATTRwt amyloidosis were older and had a higher mean LV ejection fraction compared with males. Although there were signs of sex-related differences in cardiac involvement, the relatively low number of females in this analysis may have limited the ability to draw firmer conclusions.

Cardiac morphometry in healthy young Indian adult males: An evaluation of chamber thickness and left ventricular cardiac mass

Introduction: Measurement of cardiac chambers is an important tool in the assessment of cardiac disease. Cardiac imaging can be used for the accurate assessment of these parameters. The primary objective of this study is to estimate various clinically relevant cardiac measurements including the left ventricular (LV) myocardial mass using cardiac magnetic resonance imaging (CMRI). The secondary objective is to correlate these measurements with the patient's body mass index (BMI). Material and Methods: A descriptive cross-sectional observational study was done at a tertiary care hospital. A total of 100 healthy young Indian adult males between 18 and 30 years of age underwent cardiac MRI on a 1.5Tesla Magnetic Resonance Imaging scanner. The thickness of various cardiac chambers and LV cardiac mass was measured. The results were compared with BMI. Results: Mean left atrial wall thickness is 1.6 mm in End -systole (ES)) and 1.5 mm in end diastole (ED). Mean Right atrial thickness is 1.5 mm (ES) and 1.8 mm (ED). Mean left ventricular wall thickness is 17.7 mm in End -systole (ES)) and 10.9 mm in end diastole (ED). Mean Right ventricular thickness is 6.9 mm (ES) and 3.2 mm (ED). Mean interventricular wall thickness is 14/9.7 mm in ES and ED, respectively. LV cardiac mass is 119.97 g. There is weak-to-moderate association between cardiac chambers and BMI. Discussion and Conclusion: Assessment of cardiac chamber thickness and LV cardiac mass in healthy adults can be made using CMRI. These values can be used as baseline to compare with measurements in various diseases of the heart.

Exploration of electrocardiographic and echocardiographic findings to screen transthyretin amyloid cardiomyopathy in patients with mild left ventricular hypertrophy

Abstract Background The transthyretin amyloid cardiomyopathy (ATTR-CM), a common condition in the elderly, is a life-threatening disease; however, it is treatable. The early accurate diagnosis is, therefore, an important key to improve the patient's outcomes. Electrocardiography and echocardiography are instant diagnostic tools with red flags for the screening of the ATTR-CM. In fact, ATTR-CM often mimics left ventricular hypertrophy (LVH), and the differential diagnosis is difficult to establish. Thus, the characteristics of cardiac amyloidosis may be obscured in ATTR-CM patients with mild LVH, possibly making the disease difficult to diagnose. Therefore, in this study, the effect of LVH on the occurrence of electrocardiographic and echocardiographic parameters for ATTR-CM was investigated, and their incremental value over the age for the screening of ATTR-CM in the patients with mild LVH was recorded. Methods This study retrospectively studied 319 consecutive nonischemic LVH patients with a sinus rhythm who underwent detailed diagnostic tests. The light chain-associated amyloidosis was an exclusion criterion. The mean left ventricular wall thickness (MWT) &amp;lt;12 mm was defined as mild LVH, while MWT ≥12 mm was defined as moderate to severe LVH. The ATTR-CM was diagnosed with biopsy or 99 mTc-PYP scintigraphy. The elderly were defined as people aged ≥65 years in males and ≥70 years in females, according to the literature. Each electrocardiographic and echocardiographic parameter was binarized with an external cut-off point to increase the external validity, being the incremental benefit of each parameter over age for identifying ATTR-CM assessed using a receiver operating characteristic curve analysis and comparisons of the area under the curve (AUC). Results Fourteen patients (8%) among the 170 patients with mild LVH had ATTR-CM, while 27 patients (18%) among the 149 patients with moderate to severe LVH had ATTR-CM. The patients with mild LVH had fewer electrocardiographic and echocardiographic parameters, showing a significant difference between ATTR-CM and non-ATTR-CM patients than those with moderate to severe LVH (Table 1). Among several binarized parameters, the voltage-to-mass ratio, E/A ratio, the global longitudinal strain, and also the relative apical sparing pattern demonstrated additive value for identifying the ATTR-CM over aging (Table 2). In addition, the discriminative ability of the propensity score calculated from these four variables and age was considered excellent for the screening of ATTR-CM (AUC = 0.98). Conclusion The patients with mild LVH appear to have fewer electrocardiographic and echocardiographic specific findings of the ATTR-CM compared to patients with moderate to severe LVH. However, several red flags may be useful for screening ATTR-CM even in patients with a mild LVH. Funding Acknowledgement Type of funding sources: None. Table 1Table 2

Clinical characterisation of hypertrophic cardiomyopathy caused by MYH7 gene variants in children

Abstract Background Variants in the cardiac Beta Myosin Heavy chain 7 gene (MYH7) are a common cause of hypertrophic cardiomyopathy (HCM) in adults, but their role in paediatric-onset HCM has not been systematically characterised. This study aims to describe the presentation, clinical characteristics and outcomes of childhood HCM secondary to disease-causing MYH7 variants. Methods Retrospective, longitudinal, data from 70 individuals meeting diagnostic criteria for HCM under the age of 18 years with disease-causing MYH7 variants from a single specialist centre (1991–2019) were collected. A Major Adverse Cardiac Event was defined as sudden cardiac death (SCD), heart failure-related death, cardiac transplantation, haemodynamically-compromising sustained ventricular arrhythmia or appropriate implantable cardioverter defibrillator (ICD) therapy. Results Median age at diagnosis was 9.2 years (IQR 4.2–13.3 years); 47 patients (67.1%) were less than 12 years and 7 (10.0%) were under the age of 1 at diagnosis. Twenty-two patients (31.4%) were probands. MYH7 variants were missense (n=67) or truncating (n=1). Reason for presentation were: family screening (n=45, 64.3%); cardiac symptoms (n=12, 17.1%); incidental finding (n=11, 15.7%); and out of hospital cardiac arrest (n=2, 2.9%). At baseline, mean maximum left ventricular wall thickness (MLVWT) z-score was 9.6 (±5.8), 11 patients (15.7%) had resting left ventricular outflow tract obstruction (left ventricular outflow tract gradient ≥30mmHg). Baseline phenotype did not significantly differ between probands and non-probands (MLVWT Z score 11.9 (±4.5) vs 8.5 (±6.1), p-value 0.0675). Over a median follow up of 3.6 years (IQR 1.8–7.9 years), 10 patients (14.3%) underwent a left ventricular septal myectomy at a median age 6.4 years (IQR 3.4–12.1 years) and 27 (38.6%) had an implantable cardioverter defibrillator (ICD) for primary (n=24, 34.3%) or secondary (n=3, 4.3%) prevention. Three patients (4.3%) died (SCD, n=1; heart-failure related, n=1; non-cardiac, n=1) and 3 (4.3%) underwent cardiac transplantation. Ten patients (14.3%) experienced a MACE. Patients who experienced a MACE were more likely to be probands [n= 6 (60.0%) vs n=16 (26.7%); p=0.036] but did not differ in terms of baseline phenotype (p=0.134). Conclusion MYH7 variants can cause infantile and childhood-onset disease, which is associated with significant early cardiac morbidity and mortality. Adverse outcomes were more common in those presenting as probands. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Medical Research Council, Great Ormond Street Hospital charity.

Serial scanning with 99mTc-3, 3-diphosphono-1, 2-propanodicarboxylic acid (99mTc-DPD) for early detection of cardiac amyloid deposition and prediction of clinical worsening in subjects carrying a transthyretin gene mutation

BackgroundTo determine the capability of 99mTc-DPD scintigraphy to detect early cardiac involvement and predict clinical worsening in transthyretin (TTR) gene mutation patients. MethodsEleven mutated subjects with normal interventricular septum (IVS) thickness, NT-proBNP level and no cardiac symptoms underwent three seriate 99mTc-DPD scans (visually and semiquantitatively analyzed), and was followed-up for 5-8-years. ResultsSix patients showed no myocardial accumulation in all scans. Increased IVS thickness occurring in one patient 4 years after the last scan was the only abnormal finding in these patients; no cardiac symptoms developed during the follow-up. In three patients, cardiac radiotracer uptake was found at enrollment; other laboratory/instrumental abnormal findings occurred later and cardiac symptoms developed during the follow-up period. Two patients had a negative 99mTc-DPD scan at enrollment and showed cardiac uptake in the following scans. Increased mean left-ventricular (LV) wall thickness was found 3 years after positive scintigraphy; NT-proBNP increased later in one patient. These patients developed cardiac symptoms during the follow-up period. Conclusions99mTc-DPD scan detects cardiac involvement in subjects with TTR gene mutation earlier than ECG, echocardiography and biochemical markers, occurring some years before the fulfillment of current diagnostic criteria for cardiac amyloidosis. A positive 99mTc-DPD scan predicts cardiac symptoms onset.

Sex-Related Risk of Cardiac Involvement in Hereditary Transthyretin Amyloidosis: Insights From THAOS

ObjectivesBecause patients with ATTRv cardiomyopathy are more likely to be male, this analysis aimed to increase information on associations between sex and genotype, phenotype, and degree of myocardial involvement in ATTRv amyloidosis. BackgroundTransthyretin amyloid cardiomyopathy is a progressive, fatal disease that occurs due to accumulation of wild-type or variant (ATTRv) transthyretin amyloid fibrils in the myocardium. MethodsThe Transthyretin Amyloidosis Outcomes Survey (THAOS) is an ongoing global longitudinal observational survey of patients with ATTR amyloidosis and asymptomatic carriers with TTR mutations. Data from THAOS (data cutoff: January 6, 2020) were analyzed to determine any sex-based differences in genotype, phenotype, and presence of cardiac and neurological symptoms in patients with ATTRv amyloidosis and in patients with ATTRv amyloidosis and cardiomyopathy. ResultsThere were 2,790 patients with ATTRv amyloidosis enrolled in THAOS, with male patients more likely to have symptoms of cardiac involvement and a cardiac phenotype. Male prevalence was greater in patients with more severe cardiac manifestations of disease, as assessed with N-terminal pro–B-type natriuretic peptide, left-ventricular (LV) ejection fraction, mean LV wall thickness divided by height, and LV mass index divided by height. Sex, age at disease onset, and genotype category were identified by multivariate analyses as risk factors for the development of cardiomyopathy (defined as increased LV septum thickness divided by height). ConclusionsIn this analysis, myocardial involvement was more frequent and pronounced in male patients with ATTRv amyloidosis, suggesting that there may be biological characteristics that inhibit myocardial amyloid infiltration in females or facilitate it in males.